Heterocyclic potassium channel inhibitors

Abstract

The present invention relates to a class of heterocyclic compounds of Formula I that are useful as potassium channel inhibitors to treat autoimmune disorders, cardiac arrhythmias, and the like.

What is claimed is:  
     
       1. A compound of structural Formula I:                    
       or a pharmaceutically acceptable salt, crystal form, or hydrate, wherein: 
       n is: 0, 1, 2 or 3;  
       r is: 0 or 1;  
       s is: 0 or 1;  
       R 1 , R 2 , R 6  and R 7  are independently:  
       (1) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (2) hydroxy,  
       (3) (C 1 -C 6 )-alkyl,  
       (4) HO(C 1 -C 6 )-alkyloxy,  
       (5) (C 1 -C 4 )-perfluoroalkyl,  
       (6) (C 2 -C 6 )-alkenyl,  
       (7) (C 2 -C 6 )-alkynyl,  
       (8) O[(C═O)O r ] s (C 1 -C 6 )-alkyl,  
       (9) (C 1 -C 6 )-alkyl-S(O) n —,  
       (10) [(C═O)O r ] s -aryl, wherein aryl is as defined below,  
       (11) aryloxy, wherein aryl is as defined below,  
       (12) cyano,  
       (13) nitro,  
       (14) CO 2 H,  
       (15) CO(C 1 -C 6 )-alkyl,  
       (16) CO 2 (C 1 -C 6 )-alkyl,  
       (17) CONR 8 R 9 ,  
       (18) NR 8 R 9 ,  
       (20) (C 2 -C 6 )-alkenyloxy,  
       (21) O[(C═O)O r ] s (C 1 -C 6 )-akyl-aryl,  
       (22) hydrogen,  
       (23) OCF 3 ,  
       (24) [(C═O)O r ] s (C 1 -C 6 )-alkyl-aryl,  
       (25) S(O) n —NR 8 R 9 ,  
       (26) (C 1 -C 3 )-alky-O—N═C(CH 3 )(aryl), wherein aryl is as defined below, or  
       (27) R 1  and R 2  or R 6  and R 7  can an be taken together when they are on adjacent carbons to form a fused benzo, dihydrofuranyl, furanyl, pyrrolidyl, dihydropyriolidyl, 1,3-dioxolan group,                    
       R 3  and R 4  are independently:  
       (1) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (2) hydroxy,  
       (3) HO(C 1 -C 6 )-alkyloxy,  
       (4) (C 1 -C 4 )-perfluoroalkyl,  
       (5) O(CO)CCl 3 ,  
       (6) (C 1 -C 6 )-alkyl-S(O) n —,  
       (7) phenyl-(CH 2 ) r -S(O) n —,  
       (8) cyano,  
       (9) nitro,  
       (10) CO 2 H,  
       (11) CO(C 1 -C 6 )-alkyl,  
       (12) CO 2 (C 1 -C 6 )-alkyl,  
       (13) CONR 8 R 9 ,  
       (14) NR 8 R 9 ,  
       (15) O(CO)NR 8 R 9 ,  
       (16) azido,  
       (17) NR 8 (CO)NR 8 R 9 ,  
       (18) hydrogen,  
       (19) (C 1 -C 10 )-alkyl, wherein alkyl includes cyclic as well as acyclic groups and is unsubstituted or substituted with one, two or three of the substituents selected from the group consisting of:  
       (a) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (b) hydroxy,  
       (c) oxo,  
       (d) O[(C═O)O r ] s (C 1 -C 6 )-alkyl,  
       (e) (C 1 -C 6 )-alkyl-S(O) n —,  
       (f) aryl-(C 1 -C 6 )-alkyloxy,  
       (g) cyano,  
       (h) nitro,  
       (i) vinyl,  
       (j) NR 8 R 9 ,  
       (k) O(CO)NR 8 R 9 ,  
       (l) CHO,  
       (m) CO 2 H,  
       (n) CO(C 1 -C 6 )-alkyl,  
       (o) CO 2 (C 1 -C 6 )-alkyl,  
       (p) CONR 8 R 9 ,  
       (q) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with one, two or three of the substituents selected from the group consisting of:  
       (a′) halo, as defined above,  
       (b′) hydroxy,  
       (c′) (C 1 -C 6 )-alkyl,  
       (d′) (C1-C4)-perfluoroalkyl,  
       (e′) (C 2 -C 6 )-alkenyl,  
       (f′) (C 2 -C 6 )-alkynyl,  
       (g′) (C 1 -C 6 )-alkyloxy,  
       (h′) (C 1 -C 6 )-alkyl-S(O) n —,  
       (i′) phenyl,  
       (j′) O(C 0 -C 6 )-alkyl-phenyl,  
       (k′) cyano,  
       (l′) nitro,  
       (m′) CO 2 H,  
       (n′) CO (C 1 -C 6 )-alkyl,  
       (o′) CO 2 (C 1 -C 6 )-alkyl,  
       (p′) CONR 8 R 9 ,  
       (q′) NR 8 R 9 ,  
       (r′) methylenedioxyl, and  
       (s′) OCF 3 ,  
       (r) heteroaryl, wherein heteroaryl is defined as an unsubstituted, monosubstituted, or disubstituted five or six membered aromatic heterocycle containing from 1 to 3 heteroatoms selected from the group consisting of O, N and S and wherein the substituents are members selected from the group consisting of:  
       (a′) halo, as defined above,  
       (b′) hydroxy,  
       (c′) (C 1 -C 6 )-alkyl,  
       (d′) (C1-C4)-perfuoroalkyl,  
       (e′) (C 2 -C 6 )-alkenyl,  
       (f′) (C 2 -C 6 )-alkynyl,  
       (g′) (C 1 -C 6 )-alkyloxy,  
       (h′) (C 1 -C 6 )-alkyl-S(O) n —,  
       (i′) phenyl,  
       (j′) phenoxy,  
       (k′) cyano,  
       (l′) nitro,  
       (m′) CO 2 H,  
       (n′) CO(C 1 -C 6 )-alkyl,  
       (o′) CO 2 (C 1 -C 6 )-alkyl,  
       (p′) CONR 8 R 9 ,  
       (q′) NR 8 R 9 , and  
       (r′) fused benzo or pyridyl group,  
       (s) heterocyclyl, wherein heterocyclyl is defined as a 3 to 7 atom cyclic, non-aromatic substituent containing from 1 to 3 heteroatoms selected from the group consisting of O, N, and S, said heterocycle being unsubstituted or substituted with one, two or three substituents selected from the group consisting of:  
       (a′) halo, as defined above,  
       (b′) hydroxy,  
       (c′) (C 1 -C 6 )-alkyl,  
       (d′) (C1-C4)-perfuoroalkyl,  
       (e′) (C 2 -C 6 )-alkenyl,  
       (f′) (C 2 -C 6 )-alkynyl,  
       (g′) (C 1 -C 6 )-alkyloxy,  
       (h′) (C 1 -C 6 )-alkyl-S(O) n —,  
       (i′) phenyl,  
       (j′) phenoxy,  
       (k′) cyano,  
       (l′) nitro,  
       (m′) CO 2 H,  
       (n′) CO(C 1 -C 6 )-alkyl,  
       (o′) CO 2 (C 1 -C 6 )-alkyl,  
       (p′) CONR 8 R 9 ,  
       (q′) NR 8 R 9 ,  
       (r′) NR 8 CO(C 1 -C 6 )-alkyl,  
       (s′) oxo,  
       (t′) thioxo,  
       (u′) fused benzo, and  
       (v′) fused pyridyl group;  
       (t) benzyl-S(O) n —,  
       (u) O[(C═O)O r ] s (C 2 -C 6 )-alkeny,  
       (w) O[(C═O)O r ] s heteroaryl,  
       (x) O(CH 2 ) n heteroaryl,  
       (y) O(CH 2 ) n aryl,  
       (z) fused benzo,  
       (aa) CF 3 ,  
       (bb) ═N—O-(C 1 -C 6 )alkyl-CO 2 -(C 1 -C 3 )alkyl,  
       (cc) S(O) n —(C 0 -C 6 )alkyl-aryl, wherein aryl is as defined above, or  
       (dd) S(O) n —(C 0 -C 6 )alkyl-heteroaryl, wherein heteroaryl is as defined above,  
       (20) (C 2 -C 10 )-alkenyl, wherein alkenyl is unsubstituted or substituted with one or two of the substituents selected from the group consisting of:  
       (a) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (b) hydroxy,  
       (c) oxo,  
       (e) (C 1 -C 6 )-alkyl-S(O) n —,  
       (f) phenyl-(C 1 -C 6 )-alkyloxy,  
       (g) cyano,  
       (h) nitro,  
       (i) NR 8 R 9 ,  
       (j) CHO,  
       (k) CO 2 H,  
       (l) CO(C 1 -C 6 )-alkyl,  
       (m) CO 2 (C 1 -C 6 )-alkyl,  
       (n) CONR 8 R 9 ,  
       (o) aryl, wherein aryl is as defined above,  
       (p) heteroaryl, wherein heteroaryl is as defined above,  
       (q) heterocyclyl, wherein heterocyclyl is as defined above,  
       (r) O[(C═O)O r ] s (C 1 -C 6 )-alkyl, alkyl as defined above,  
       (s) O[(C═O)O r ] s (C 2 -C 6 )-alkenyl, as defined above,  
       (t) O[(C═O)O r ] s aryl, aryl as defined above,  
       (u) O[(C═O)O r ] s heteroaryl, heteroaryl as defined above,  
       (v) O(CH 2 ) n heteroary, heteroaryl as defined above, and  
       (w) O(CH 2 ) n aryl, aryl as, defined above;  
       (21) (C 2 -C 10 )-alkynyl, wherein alkynyl is unsubstituted or substituted with one or two of the substituents selected from the group consisting of:  
       (a) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (b) bydroxy,  
       (c) oxo,  
       (d) (C 1 -C 6 )-alkyloxy,  
       (e) (C 1 -C 6 )-S(O) n —,  
       (f) phenyl-(C 1 -C 6 )-alkyloxy,  
       (g) cyano,  
       (h) nitro,  
       (i) vinyl,  
       (j) NR 8 R 9 ,  
       (k) NR 8 CO(C 1 -C 6 )-alkyl,  
       (l) CHO,  
       (m) CO 2 H,  
       (n) CO(C 1 -C 6 )-alkyl,  
       (o) CO 2 C(C 1 -C 6 )-alkyl,  
       (p) CONR 8 R 9 ,  
       (q) aryl, wherein aryl is as defined above,  
       (r) heteroaryl, wherein heteroaryl is as defined above,  
       (s) heterocyclyl, wherein heterocyclyl is as defined above,  
       (t) O[(C═O)O r ] s (C 1 -C 6 )-alkyl, alkyl as defined above,  
       (u) O[(C═O)O r ] s (C 2 -C 6 )-alkenyl, as defined above,  
       (v) O[(C═O)O r ] s aryl, aryl as defined above,  
       (w) O[(C═O)O r ] s heteroaryl, heteroaryl as defined above  
       (x) O(CH 2 ) n heteroaryl, heteroaryl as defined above, and  
       (y) O(CH 2 ) n aryl, aryl as defined above,  
       (22) O[(C═O)O r ] s (C 1 -C 6 )-alkyl, alkyl as defined above,  
       (23) O[(C═O)O r ] s (C 2 -C 6 )-alkenyl, as defined above,  
       (24) O[(C═O)O r ] s aryl, aryl as defined above,  
       (25) O[(C═O)O r ] s heteroaryl, heteroaryl as defined above  
       (26) O(CH 2 ) n heteroary, heteroaryl as defined above,  
       (27) aryl, wherein aryl is as defined above,  
       (28) O(CH 2 ) n aryl, aryl as defined above,  
       (29) oxo,  
       (30) ═CH-(C1-C6)-alkyl, wherein alkyl is as defined above,  
       (31) ═CH-(C2-C6)-alkenyl, wherein alkenyl is as defined above,  
       (32) ═CH-aryl, wherein aryl is as defined above, or  
       (33) ═CH 2 ;  
       R 5  is:  
       (1) [(C═O)O r ] s (C 2 -C 10 )-alkenyl, wherein alkenyl is as defined above,  
       (2) [C(═O)O](C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above in R 3  and R 4 ,  
       (3) (C═O)(C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above in R 3  and R 4 ,  
       (4) (C 1 -C 10 )-alkyl, wherein when R 5  is C 4 -alkyl, R 3  and R 4  are not both hydrogen or when R 5  is C 4 -alkyl and one of R 3  or R 4  is methyl, the other R 3  or R 4  is not hydrogen or methyl,  
       (5) hydroxy,  
       (6) [(C═O)O r ] s aryl, wherein aryl is as defined above,  
       (7) oxo,  
       (8) (C═O) r S(O) n (C 1 -C 8 )-alkyl, wherein alkyl is as defined above,  
       (9) (C═O) r S(O) n aryl, wherein aryl is as defined above,  
       (10) (C═O) r S(O) n heteroayl, wherein heteroarylaryl is as defined above,  
       (11) (C═O)(C 1 -C 6 )-alkyl-pentafluorobenzene, or  
       (12) [(C═O)O r ] s heteroaryl, wherein heteroaryl is as defined above;  
       R 8  and R 9  are independently selected from the group consisting of:  
       (1) hydrogen,  
       (2) [(C═O)O r ] s aryl, wherein aryl is as defined above,  
       (3) [(C═O)O r ] s (C 2 -C 8 )-alkenyl, wherein alkenyl is as defined above,  
       (4) [(C═O)O r ] s (C 1 -C 8 )-alkyl, wherein alkyl is as defined above,  
       (5) (C═O) r S(O) n (C 1 -C 8 )-alkyl, wherein alkyl is as defined above,  
       (6) (C═O) r S(O) n aryl, wherein aryl is as defined above, and  
       (7) heterocyclyl, wherein heterocyclyl is defined above,  
       or R 8  and R 9  can be linked to make one of the following with the nitrogen to which they are bound:                    
       R 10  is:  
       (1) hydrogen,  
       (2) [(C═O)O r ] s aryl, wherein aryl is as defined above, or  
       (3) [(C═O)O r ] s (C 1 -C 6 )-alkyl, wherein alkyl is as defined above.  
     
     
       2. The compound of claim  1 , wherein: 
       R 1 , R 2 , R 6  and R 7  are independently:  
       (1) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (2) hydroxy,  
       (3) (C 1 -C 3 )-alkyl,  
       (4) (C 1 -C 4 )-perfluoroalkyl,  
       (5) O[(C═O)O r ] s (C 1 -C 3 )-alkyl, wherein the alkyl may be cyclic or straight-chained,  
       (6) CO 2 H,  
       (7) CO(C 1 -C 3 )-alkyl,  
       (8) CO 2 (C 1 -C 3 )-alkyl,  
       (9) hydrogen,  
       (10) OCF 3 , or  
       (11) R 1  and R 2  or R 6  and R 7  can an be taken together to form a fused benzo, dihydrofuranyl, furanyl, pyrrolidyl, dihydropyrrolidyl or 1,3-dioxolan group;  
       R 3  and R 4  are independently:  
       (1) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (2) hydroxy,  
       (3) HO(C 1 -C 3 )-alkyloxy,  
       (4) (C 1 -C 4 )-perfluoroalkyl,  
       (5) O(CO)CCl 3 ,  
       (6) (C 1 -C 3 )-alkyl-S(O) n —,  
       (7) phenyl-(CH 2 ) r -S(O) n —,  
       (8) cyano,  
       (9) nitro,  
       (10) CO 2 H,  
       (11) CO(C 1 -C 3 )-alkyl,  
       (12) CO 2 (C 1 -C 3 )-alkyl,  
       (13) CONR 8 R 9 ,  
       (14) NR 8 R 9 ,  
       (15) O(CO)NR 8 R 9 ,  
       (16) azido,  
       (17) NR 8 (CO)NR 8 R 9 ,  
       (18) hydrogen,  
       (19) (C 1 -C 6 )-alkyl, wherein alkyl includes cyclic as well as acyclic groups and is unsubstituted or substituted with one of the substituents selected from the group consisting of:  
       (a) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (b) hydroxy,  
       (c) oxo,  
       (d) O[(C═O)O r ] s (C 1 -C 3 )-alkyl,  
       (e) (C 1 -C 3 )-alkyl-S(O) n —,  
       (f) aryl-(C 1 -C 3 )-alkyloxy,  
       (g) cyano,  
       (h) nitro,  
       (i) NR 8 R 9 ,  
       (j) O(CO)NR 8 R 9 ,  
       (k) CHO,  
       (l) CO 2 H,  
       (m) CO(C 1 -C 3 )-alkyl,  
       (n) CO 2 (C 1 -C 6 )-alkyl,  
       (o) CONR 8 R 9 ,  
       (p) aryl, wherein aryl is defined as phenyl, unsubstituted or substituted with one or two of the substituents selected from the group consisting of:  
       (a′) halo, as defined above,  
       (b′) hydroxy,  
       (c′) (C 1 -C 3 )-alkyl,  
       (d′) (C1-C2)-perfluoroalkyl,  
       (e′) (C 2 -C 3 )-alkenyl,  
       (f′) (C 2 -C 3 )-alkynyl,  
       (g′) (C 1 -C 3 )-alkyloxy,  
       (h′) (C 1 -C 3 )-alkyl-S(O) n —,  
       (i′) phenyl,  
       (j′) phenoxy,  
       (k′) cyano,  
       (l′) nitro,  
       (m′) CO 2 H,  
       (n′) CO(C 1 -C 3 )-alkyl,  
       (o′) CO 2 (C 1 -C 3 )-alkyl,  
       (p′) CONR 8 R 9 , and  
       (q′) NR 8 R 9 ,  
       (q) O[(C═O)O r ] s (C 2 -C 6 )-alkenyl,  
       (r) O[(C═O)O r ] s aryl, and  
       (s) O(CH 2 ) n aryl;  
       (20) (C 2 -C 6 )-alkenyl, wherein alkenyl is unsubstituted or substituted with one of the substituents selected from the group consisting of:  
       (a) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (b) hydroxy,  
       (c) oxo,  
       (e) (C 1 -C 3 )-alkyl-S(O) n —,  
       (f) phenyl-(C 1 -C 3 )-alkyloxy,  
       (g) cyano,  
       (h) nitro,  
       (i) NR 8 R 9 ,  
       (j) CHO,  
       (k) CO 2 H,  
       (l) CO(C 1 -C 6 )-alkyl,  
       (m) CO 2 (C 1 -C 6 )-alkyl,  
       (n) CONR 8 R 9 ,  
       (o) aryl, wherein aryl is as defined above,  
       (p) heteroaryl, wherein heteroaryl is as defined above,  
       (q) heterocyclyl, wherein heterocyclyl is as defined above,  
       (r) O[(C═O)O r ] s (C 1 -C 6 )-alkyl, alkyl as defined above,  
       (s) O[(C═O)O r ] s (C 2 -C 6 )-alkenyl, as defined above,  
       (t) O[(C═O)O r ] s aryl, aryl as defined above,  
       (u) O[(C═O)O r ] s heteroaryl, heteroaryl as defined above,  
       (v) O(CH 2 ) n heteroaryl, heteroaryl as defined above, and  
       (w) O(CH 2 ) n aryl, aryl as defined above;  
       (21) O[(C═O)O r ] s (C 1 -C 6 )-alkyl, alkyl as defined above,  
       (22) O[(C═O)O r ] s (C 2 -C 6 )-alkenyl, as defined above,  
       (23) O[(C═O)O r ] s aryl, aryl as defined above,  
       (24) O[(C═O)O r ] s heteroaryl, heteroaryl as defined above  
       (25) O(CH 2 ) n heteroaryl, heteroaryl as defined above,  
       (26) aryl, wherein aryl is as defined above,  
       (27) O(CH 2 ) n aryl, aryl as defined above,  
       (28) oxo,  
       (29) ═CH-(C 1 -C 6 )-alkyl, wherein alkyl is as defined above,  
       (30) ═CH-(C 2 -C 6 )-alkenyl, wherein alkenyl is as defined above,  
       (31) ═CH-aryl, wherein aryl is as defined above, or  
       (32) ═CH 2 ;  
       R 5  is:  
       (1) [(C═O)O r ] s (C 2 -C 10 )-alkenyl, wherein alkenyl is as defined above,  
       (2) [C(═O)O](C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above in R 3  and R 4 ,  
       (3) (C═O)(C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above in R 3  and R 4 ,  
       (4) (C 1 -C 10 )-alkyl, wherein when R 5  is C 4 -alkyl, R 3  and R 4  are not both hydrogen, or when R 5  is C 4 -alkyl and one of R 3  or R 4  is methyl, the other R 3  or R 4  is not hydrogen or methyl,  
       (5) [(C═O)O r ] s aryl, wherein aryl is as defined above,  
       (6) (C═O) r S(O) n (C 1 -C 8 )-alkyl, wherein alkyl is as defined above, or  
       (7) (C═O) r S(O) n aryl, wherein aryl is as defined above;  
       R 8  and R 9  are independently selected from the group consisting of:  
       (1) hydrogen,  
       (2) [(C═O)O r ] s aryl, wherein aryl is as defined above,  
       (3) [(C═O)O r ] s (C 2 -C 8 )-alkenyl, wherein alkenyl is as defined above,  
       (4) [(C═O)O r ] s (C 1 -C 8 )-alkyl, wherein alkyl is as defined above,  
       (5) (C═O) r S(O) n (C 1 -C 8 )-alkyl, wherein alkyl is as defined above,  
       (6) (C═O) r S(O) n aryl, wherein aryl is as defined above, and  
       (7) heterocyclyl, wherein heterocycly is defined above;  
       R 10  is:  
       (1) hydrogen, or  
       (2) [(C═O)O r ] s (C 1 -C 3 )-alkyl.  
     
     
       3. The compound of claim  2 , wherein; 
       R 1 , R 2 , R 6  and R 7  are independently:  
       (1) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (2) hydroxy,  
       (3) (C 1 -C 3 )-alkyl,  
       (4) (C 1 -C 4 )-perfluoroalkyl,  
       (5) O[(C═O)O r ] s (C 1 -C 3 )-alkyl, wherein the alkyl may be cyclic or straight-chained,  
       (6) CO(C 1 -C 3 )-alkyl,  
       (7) CO 2 (C 1 -C 3 )-alkyl,  
       (8) hydrogen, or  
       (9) OCF 3 ;  
       R 3  and R 4  are independently:  
       (1) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (2) hydroxy,  
       (4) (C 1 -C 3 )-perfluoroalkyl,  
       (10) CO 2 H,  
       (11) CO(C 1 -C 3 )-alkyl,  
       (12) CO 2 (C 1 -C 3 )-alkyl,  
       (18) hydrogen,  
       (19) (C 1 -C 4 )-alkyl, wherein alkyl can be cyclic or acyclic,  
       (20) (C 2 -C 3 )-alkenyl,  
       (21) O[(C═O)O r ] s (C 1 -C 4 )-alkyl,  
       (22) O[(C═O)O r ] s (C 2 -C 4 )-alkenyl,  
       (23) O[(C═O)O r ] s aryl,  
       (26) phenyl,  
       (27) O(CH 2 )phenyl, or  
       (28) oxo;  
       R 5  is:  
       (1) [(C═O)O r ] s (C 2 -C 10 )-alkenyl, wherein alkenyl is as defined above,  
       (2) [C(═O)O](C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above,  
       (3) (C═O)(C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above,  
       (4) (C 1 -C 10 )-alkyl, wherein when R 5  is C 4 -alkyl, R 3  and R 4  are not both hydrogen, or when R 5  is C 4 -alkyl and one of R 3  or R 4  is methyl, the other R 3  or R 4  is not hydrogen or methyl,  
       (5) [(C═O)O r ] s aryl, wherein aryl is as defined above,  
       (6) (C═O) r S(O) n (C 1 -C 8 )-alkyl, wherein alkyl is as defined above, or  
       (7) (C═O) r S(O) n aryl, wherein aryl is as defined above;  
       R 10  is:  
       (1) hydrogen, or  
       (2) [(C═O)O r ] s (C 1 -C 3 )-alkyl.  
     
     
       4. The compound of claim  3 , wherein: 
       R 1 , R 2 , R 6  and R 7  are independently:  
       (1) halo, wherein halo is fluoro, chloro, bromo, or iodo,  
       (2) hydroxy,  
       (3) (C 1 -C 3 )-alkyl,  
       (4) O(C 1 -C 3 )-alkyl, wherein alkyl is cyclic or acyclic,  
       (5) O(CO)(C 1 -C 3 )-alkyl, or  
       (6) (CO)(C 1 -C 3 )-alkyl;  
       R 3  and R 4  are hydrogen;  
       R 5  is:  
       (1) [(C═O)O r ] s ](C 1 -C 10 )-alkenyl,  
       (2) [C(═O)O](C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above,  
       (3) (C═O)(C 1 -C 10 )-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above,  
       (4) (C 1 -C 10 )-alkyl, (C 1 -C 10 )-alkyl, wherein when R 5  is C 4 -alkyl, R 3  and R 4  are not both hydrogen, or when R 5  is C 4 -alkyl and one of R 3  or R 4  is methyl, the other R 3  or R 4  is not hydrogen or methyl,  
       (5) [(C═O)O r ] s aryl,  
       (6) (C═O) r S(O) n (C 1 C 8 )-alkyl, or  
       (7) (C═O) r S(O) n aryl; and  
       R 10  is:  
       (1) hydrogen, or  
       (2) (C═O)(C 1 -C 3 )-alkyl.  
     
     
       5. A compound selected from the group consisting of: 1-N-phenylacetyl-4-phenyl4-(3-(2-methoxyphenyl)-3-oxo-2-azaprop-1-yl)piperidine, and 1-N-((3-phenyl)propan-1-oyl)-4-phenyl-4-(3-(2-methoxyphenyl)-3-oxo-2-azaprop-1-yl)piperidine, or a pharmaceutically acceptable salt thereof. 
     
     
       6. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and the compound claim  1  or a pharmaceutically acceptable crystal form or hydrate thereof. 
     
     
       7. A pharmaceutical composition made by combining the compound of claim  1  and a pharmaceutically acceptable carrier. 
     
     
       8. A method of treating an immunoregulatory abnormal condition in a mammal requiring K v 1.3 voltage-gated potassium channel inhibition comprising administering a compound of claim  1  in an amount that is effective at inhibiting said K v 1.3 voltage-gated potassium channel. 
     
     
       9. The method of claim  8 , wherein the condition is an autoimmune disease. 
     
     
       10. A method of preventing or treating resistance to transplantation or transplantation rejection of organs or tissues into a patient in need thereof, which comprises administering a therapeutically effective amount of a compound of claim  1 . 
     
     
       11. A method of suppressing the immune system in a subject in need thereof, which comprises administering to the subject an immune suppressing amount of a compound of claim  1 .